Potential DMD Treatment, Pamrevlumab, Helps to Preserve Lung, Heart and Upper Limb Function in Youth, Early Trial Data Show

Early trial data supports the potential of FibroGen‘s investigative treatment pamrevlumab to slow the decline in, or even improve, lung and heart function in non-ambulatory youth with Duchenne muscular dystrophy (DMD), as well as to preserve their upper limb performance and strength.

These findings were highlighted on June 28 at the Parent Project Muscular Dystrophy (PPMD) 2019 Annual Conference held in Orlando, Florida. The presentation, “Study 079 – An Open-Label, Single-Arm Phase 2 Trial Evaluating Pamrevlumab, a Monoclonal Antibody to Connective Tissue Growth Factor (CTGF) in Non-Ambulatory Subjects with Duchenne Muscular Dystrophy (NCT02606136),” is available here.

Data presented showcases the preliminary results of an open-label, single-arm Phase 2 study (NCT02606136) assessing the safety and efficacy of pamrevlumab in treating young people with DMD unable to walk by themselves (non-ambulatory) across sites in the U.S. They were diagnosed at a median age of 5.5, and were non-ambulatory at the study’s start (its baseline) for 3.4 years.

Twenty-one boys and young men, ages 12 to 25, are enrolled and being treated with an intravenous (IV) infusion of pamrevlumab (35 mg/kg) every two weeks, which will continue up to 156 weeks (three years). They will then be followed for another four weeks.

Most participants, 57%, had a deletion in the dystrophin (DMD) gene, with the others carrying a duplication or a point mutation. All were taking corticosteroids, namely deflazacort (brand name Emflaza, marketed by PTC Therapeutics) or prednisone.

FibroGen researchers at PPMD 2019 shared an interim analysis of trial findings, conducted after all patients completed one year of treatment (52 weeks).

The data showed that pamrevlumab delayed disease worsening and lead to a “better preservation of lung function” compared to the documented normal progression of DMD (the disease’s natural history), researchers said.

At one year, spirometry results showed that treated patients had a slowing in the decline of lung function reflected by a 5.47% lesser-than-expected decline in percent predicted forced vital capacity (ppFVC), and an 8.7% lesser decline in percentage predicted forced expiratory volume in one second (ppFEV1). Both were determined in comparison to patients’ “normal progression” reported in the literature, and which served as a control group.

In people with DMD, heart muscle progressively weakens. MRIs taken of the hearts of treated patients revealed that pamrevlumab could not only slow worsening but actually improve heart function, in opposition to its expected decline. 

Specifically, compared to the study’s start, pamrevlumab was associated with an increase in the left ventricular ejection fraction percentage (LVEF%) of 0.29% and 1.79% in those with a low or a near normal ejection fraction, respectively, at one year of treatment.  LVEF is a measure of how well the left ventricle of the heart (its main pumping chamber) pumps blood to the rest of the body. 

These heart improvements correlated well with a reduction in heart scarring, which indicates that pamrevlumab could lead to a “stabilization and possible improvement in the myocardial [heart’s muscle] fibrosis burden,” the researchers wrote.

Pamrevlumab also either improved or reduced one-year changes in upper limb performance and hand grip strength, suggesting the treatment either preserved or delayed the loss of upper limb function. This was accompanied by a slowing or even a potential improvement of muscle scarring in the upper arm.

Overall, pamrevlumab was safe and well-tolerated, with most treatment-emergent adverse events (TEAEs) being mild to moderate in severity. Most common side effects were headache (66.7% of the patients), vomiting (42.9%), nasopharyngitis (swelling of the nasal passages and the back of the throat; 42.9%) cough (33.3%), and back pain (28.6%). Most of the patients experiencing TEAEs had pre-existing risk factors, and none of these events led to pamrevlumab or study discontinuation. 

Pamrevlumab (FG-3019) is a fully human monoclonal antibody that blocks the activity of connective tissue growth factor (CTGF), a central mediator of tissue remodeling and fibrosis progression. FibroGen is currently developing pamrevlumab to treat non-ambulatory DMD patients, and those with idiopathic pulmonary fibrosis (IPF) and locally advanced pancreatic cancer (LAPC).

While most disease-modifying DMD medications available or under testing are meant for patients still able to walk independently (ambulatory), pamrevlumab is being developed for those unable to walk by themselves and fill this unmet need.

The U.S. Food and Drug Administration (FDA) designated pamrevlumab an orphan drug for the possible treatment of DMD in April.